This project is designed to use recent techniques, derived from the study of leukemia virus infection of cultured cells, to attack the problem of the pathogenesis of virus-induced leukemia in mice. To discover where the virus replicates during the preleukemic period, we are measuring, by hybridization with virus-specific DNA, levels of virus-specific RNA in organs of infected mice. Preliminary experiments suggest that the virus is replicating in the thymus and spleen. The viral RNA will be localized within specific cells of relevant organs by physical separation of cells from these organs or by in situ hybridization. Once we have established the normal course of viral infection, we will reexamine key stages in this process in animals which have been treated to alter the incidence of leukemia. In the early stages of this project we discovered two virus clones which differ in the speed with which they cause leukemia. We have shown that the two virus genomes are similar in nucleic acid sequence (by RNA-DNA hybridization). In addition, we have shown that they grow equally well in mice and that they induce the appearance of xenotropic viruses equally well in infected mice. We are currently attempting to discover the difference between these viruses by comparing the proteins from purified virus preparations.